During medical treatment it is critical to maintain the circulatory concentration of drugs within their therapeutic range. A novel biosensor is presented in this work to address the lack of a ...reliable point-of-care drug monitoring system in the market. The biosensor incorporates high selectivity and sensitivity by integrating aptamers as the recognition element and field-effect transistors as the signal transducer. The drug tenofovir was used as a model small molecule. The biointerface of the sensor is a binary self-assembled monolayer of specific thiolated aptamer and 6-mercapto-1-hexanol (MCH), whose ratio was optimized by electrochemical impedance spectroscopy measurements to enhance the sensitivity towards the specific target. Surface plasmon resonance, performed under different buffer conditions, shows optimum specific and little non-specific binding in phosphate buffered saline. The dose-response behavior of the field-effect biosensor presents a linear range between 1 nM and 100 nM of tenofovir and a limit of detection of 1.2 nM. Two non-specific drugs and one non-specific aptamer, tested as stringent control candidates, caused negligible responses. The applications were successfully extended to the detection of the drug in human serum. As demonstrated by impedance measurements, the aptamer-based sensors can be used for real-time drug monitoring.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Electrochemical sensors have found a wide range of applications in analytical chemistry thanks to the advent of high-throughput printing technologies. However, these techniques are usually limited to ...two-dimensional (2D) geometry with relatively large minimal feature sizes. Here, we report on the scalable fabrication of monolithically integrated electrochemical devices with novel and customizable fiber-based architectures. The multimaterial thermal drawing technique is employed to co-process polymer composites and metallic glass into uniform electroactive and pseudoreference electrodes embedded in an insulating polymer cladding fiber. To demonstrate the versatility of the process, we tailor the fiber microstructure to two configurations: a small-footprint fiber tip sensor and a high-surface-area capillary cell. We demonstrate the performance of our devices using cyclic voltammetry and chronoamperometry for the direct detection and quantification of paracetamol, a common anesthetic drug. Finally, we showcase a fully portable pipet-based analyzer using low-power electronics and an “electrochemical pipet tip” for direct sampling and analysis of microliter-range volumes. Our approach paves the way toward novel materials and architectures for efficient electrochemical sensing to be deployed in existing and novel personal care and surgical configurations.
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IJS, KILJ, NUK, PNG, UL, UM
•We explore travel demand, modal shift, efficiency and fuel paths in global IAMs.•Baseline scenarios follow historic trends, with activity and efficiency increase.•Technology change, affecting carbon ...intensity, is needed to mitigate emissions.•Policy affecting service demand have limited contribution to emission reduction.•These policies could complement the current radical technology switch required.
The transport sector is growing fast in terms of energy use and accompanying greenhouse gas emissions. Integrated assessment models (IAMs) are used widely to analyze energy system transitions over a decadal time frame to help inform and evaluating international climate policy. As part of this, IAMs also explore pathways of decarbonizing the transport sector. This study quantifies the contribution of changes in activity growth, modal structure, energy intensity and fuel mix to the projected passenger transport carbon emission pathways. The Laspeyres index decomposition method is used to compare results across models and scenarios, and against historical transport trends. Broadly-speaking the models show similar trends, projecting continuous transport activity growth, reduced energy intensity and in some cases modal shift to carbon-intensive modes - similar to those observed historically in a business-as-usual scenario. In policy-induced mitigation scenarios further enhancements of energy efficiency and fuel switching is seen, showing a clear break with historical trends. Reduced activity growth and modal shift (towards less carbon-intensive modes) only have a limited contribution to emission reduction. Measures that could induce such changes could possibly complement the aggressive, technology switch required in the current scenarios to reach internationally agreed climate targets.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
•Cytotoxic anticancer drugs are increasingly recognized to be valid candidates for therapeutic drug monitoring (TDM).•Numerous LC-MS/MS methods have been developed to that end for the quantification ...in patients’ plasma samples of single or combination of chemotherapeutic drugs.•However, there is a need for a more systematic use of stable isotopically labelled internal standards of cytotoxic drugs to circumvent patients’ biological matricesvariability, that would increase the reliability of cytotoxic drugs quantification.•LC-MS/MS assays can accommodate multiplexed analyses of cytotoxic drugs with optimal selectivity and specificity as well as short analytical times. Yet, there is still several organisational and clinical constraints to address before TDM of cytotoxic drugs could be more largely adopted.
In the era of precision medicine, there is increasing evidence that conventional cytotoxic agents may be suitable candidates for therapeutic drug monitoring (TDM)- guided drug dosage adjustments and patient’s tailored personalization of non-selective chemotherapies. To that end, many liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) assays have been developed for the quantification of conventional cytotoxic anticancer chemotherapies, that have been comprehensively and critically reviewed. The use of stable isotopically labelled internal standards (IS) of cytotoxic drugs was strikingly uncommon, accounting for only 48 % of the methods found, although their use could possible to suitably circumvent patients’ samples matrix effects variability. Furthermore, this approach would increase the reliability of cytotoxic drug quantification in highly multi-mediated cancer patients with complex fluctuating pathophysiological and clinical conditions. LC-MS/MS assays can accommodate multiplexed analyses of cytotoxic drugs with optimal selectivity and specificity as well as short analytical times and, when using stable-isotopically labelled IS for quantification, provide concentrations measurements with a high degree of certainty. However, there are still organisational, pharmacological, and medical constraints to tackle before TDM of cytotoxic drugs can be more largely adopted in the clinics for contributing to our ever-lasting quest to improve cancer treatment outcomes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Obstructive Jaundice: Thinking Beyond the Bilio-Pancreatic Khalaf, Kareem; Koleth, G.; Spadaccini, M. ...
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... et al.,
11/2022, Volume:
22
Journal Article
Peer reviewed
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This paper reports the characterization of an electrochemical biosensor for the continuous monitoring of Naproxen based on cytochrome P450. The electrochemical biosensor is based on the drop-casting ...of multi-walled carbon-nanotubes (MWCNTs) and microsomal cytochrome P4501A2 (msCYP1A2) on a graphite screen-printed electrode (SPE). The proposed biosensor was employed to monitor Naproxen (NAP), a well-known anti-inflammatory compound, through cyclic voltammetry. The dynamic linear range for the amperometric detection of NAP had an upper limit of 300 µM with a corresponding limit of detection (LOD) of 16 ± 1 µM (S/N=3), which is included in NAP physiological range (9-300 µM). The MWCNT/msCYP1A2-SPE sensor was also calibrated for NAP detection in mouse serum that was previously extracted from mice, showing a slightly higher LOD (33 ± 18 µM). The stability of the msCYP1A2-based biosensor was assessed by longtime continuous cyclic voltammetric measurements. The ability of the sensor to monitor drug delivery was investigated by using a commercial micro-osmotic pump. Results show that the MWCNT/msCYP1A2-SPE sensor is capable of precisely monitoring the real-time delivery of NAP for 16 h. This work proves that the proposed electrochemical sensor might represent an innovative point-of-care solution for the personalization of drug therapies, as well as for pharmacokinetic studies in both animals and humans.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Ampullary carcinoma (AC) is histologically classified as intestinal (In-AC), pancreaticobiliary (Pb-AC) or mixed-AC. The prognostic role of AC subtypes has been debated and remains unclear. The aims ...of this study were to evaluate outcomes after pancreatoduodenectomy (PD) for each subtype of AC and to compare these with pancreatic ductal adenocarcinoma PDAC and distal cholangiocarcinoma DCC.
PDs performed for AC between 2010 and 2018 were retrospectively evaluated. Histological subtype was obtained for all patients. One-year, 3-year and 5-year disease-free-survival (DFS) and overall survival (OS) rates were calculated. Kaplan-Meier survival analysis was performed to compare Pb-AC, In-AC and mixed-AC. Comparison with PDs performed for PDAC and DCC during the same period was also performed.
A total of 97 patients undergoing PD for AC were evaluated: 34 (35.1%) In-AC, 54 (55.7%) Pb-AC and 9 mixed-AC (9.3%). DFS and OS rates for Pb-AC were significantly lower compared to In-AC (p < 0.05 and p < 0.01), but similar to mixed-AC (p = 0.3 and p = 0.4). Adjuvant therapy was not associated with increased survival, regardless of the histological subtype (p > 0.05). During the same period, 337 and 53 PDs for PDAC and DCC, respectively, were performed. In-AC was associated with significantly better outcomes compared to PDAC and DCC (p < 0.001); DFS and OS rates for Pb-AC and mixed AC were significantly higher compared to PDAC (p < 0.001), but similar to DCC (p > 0.05).
Pb-AC has significantly worse survival compared to In-AC. Moreover, mixed-AC should be considered as Pb-AC. Pb-AC and mixed-AC seem to have better prognosis compared to PDAC, but similar to DCC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Silicon nanowires (SiNWs), fabricated via a top-down approach and then functionalized with biological probes, are used for electrically-based sensing of breast tumor markers. The SiNWs, featuring ...memristive-like behavior in bare conditions, show, in the presence of biomarkers, modified hysteresis and, more importantly, a voltage memory component, namely a voltage gap. The voltage gap is demonstrated to be a novel and powerful parameter of detection thanks to its high-resolution dependence on charges in proximity of the wire. This unique approach of sensing has never been studied and adopted before. Here, we propose a physical model of the surface electronic transport in Schottky barrier SiNW biosensors, aiming at reproducing and understanding the voltage gap based behavior. The implemented model describes well the experimental I-V characteristics of the device. It also links the modification of the voltage gap to the changing concentration of antigens by showing the decrease of this parameter in response to increasing concentrations of the molecules that are detected with femtomolar resolution in real human samples. Both experiments and simulations highlight the predominant role of the dynamic recombination of the nanowire surface states, with the incoming external charges from bio-species, in the appearance and modification of the voltage gap. Finally, thanks to its compactness, and strict correlation with the physics of the nanodevice, this model can be used to describe and predict the I-V characteristics in other nanostructured devices, for different than antibody-based sensing as well as electronic applications.
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